Laser Microdissection LMD7 System enables users to isolate specific single cells or entire areas of tissue. This system allows rapid and accurate microdissection of both small and large groups of cells and can be used with phase contrast for live-cell applications, with stained tissue samples and transmitted light, or with epi- fluorescence for fluorescence tagged targets. Powered by a unique laser design and dynamic software, Leica LMD7 systems allow users to easily isolate Regions of Interest (ROI) from entire areas of tissue down to single cells or even subcellular structures such as chromosomes. Our VA researchers in hepatology, gastroenterology, cholangiocytes biology and diabetic pathology rely on this method. Furthermore, LMD7 system is a perfect tool for live cell culture (LCC), for cloning and re-cultivation, manipulation or downstream analysis. At the Richard L. Roudebush VA Medical Center (RRVA) at Indianapolis, increased interactions and collaborations have been established among multiple investigators with expertise in liver and cholangiocytes pathobiology, neuropathology, cancer biology, cardiovascular pathophysiology, diabetes and bone metabolism. With the purchase of the shared equipment of the Leica Laser Capture Microdissection system LMD7, which can be used by investigators of different disciplines for the single cell analysis in human healthy and diseased tissues and cells, such collaborations could be further enhanced. Several of the proposed users are focused on chronic liver disorders such as alcoholic liver diseases; Non-alcoholic fatty liver disease (NAFLD), cholestatic liver diseases, hepatitis B and C virus infections are severe medical disorders and will further develop to liver fibrosis, cirrhosis and liver cancer. They are the 10th leading cause of death in the United States that are highly relevant to our veterans. The study shows that the hazard of developing chronic liver diseases and liver cancer cirrhosis in the VA health care system significantly increased recently. The translational research approach of the healthy and diseases human liver at single-cell resolution is critical to understanding the pathogenesis and treatment of human liver disease. This single cell analysis approach has been difficult to carry out, mainly because fresh human liver tissue access is scarce and the tissue is difficult to fractionate without damaging fragile resident cell populations. Cells and tissues from animals and humans that model various pathological processes have played a vital part in medical breakthroughs in the past decade that have benefited the health care of US populations including Veterans. The Leica Laser Capture Microdissection System LMD7 requested in this application will be used to study intracellular signaling and protein interactions in single human cell stage under pathological conditions of human liver and other diseases that lead to significant mortality and morbidity in the Veteran population. The long-term objective of the investigators involved in this application is to obtain a better understanding of molecular underpinnings of diseases with the ultimate goal of improving healthcare for Veterans. The requested Leica Laser Capture Microdissection LMD7 system is critical for progress in these important areas. Two specific aims are proposed in this application: Aim 1: To purchase and maintain a Leica LMD7 system for use by dedicated VA researchers. Aim 2: To enhance the quality of science and promote collaboration among dedicated VA researchers. Results of this proposed research will provide a better understanding of underlying mechanisms critical for designing new therapies for the prevention and treatment of these chronic human diseases. The Leica LMD7 system makes it possible to generate the gene profiling data at specific cell type of intact specimens. It also becomes possible to exclude incorrect results caused by mechanically isolation of the cells from the samples. Having this novel, state-of-the-art laser capture microdissection system will open up new avenues of research and collaboration at RRVA that will not be possible without it.